Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text PDF (Full Text) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JGP Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cukras, C. A. Articles by Nichols, C. G. Search for Related Content PubMed PubMed Citation Articles by Cukras, C. A. Articles by Nichols, C. G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB (L)-ALANINE POTASSIUM Social Bookmarking                      What's this?

Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110

Address all correspondence to Colin G. Nichols, Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, MO 63110. Fax: (314) 362-7463; E-mail: cnichols{at}cellbio.wustl.edu

All members of the inward rectifiier K⁺ (Kir) channel family are activated by phosphoinositides and other amphiphilic lipids. To further elucidate the mechanistic basis, we examined the membrane association of Kir6.2 fragments of K_ATP channels, and the effects of site-directed mutations of these fragments and full-length Kir6.2 on membrane association and K_ATP channel activity, respectively. GFP-tagged Kir6.2 COOH terminus and GFP-tagged pleckstrin homology domain from phospholipase C 1 both associate with isolated membranes, and association of each is specifically reduced by muscarinic m1 receptor–mediated phospholipid depletion. Kir COOH termini are predicted to contain multiple ß-strands and a conserved -helix (residues 306–311 in Kir6.2). Systematic mutagenesis of D307-F315 reveals a critical role of E308, I309, W311 and F315, consistent with residues lying on one side of a -helix. Together with systematic mutation of conserved charges, the results define critical determinants of a conserved domain that underlies phospholipid interaction in Kir channels.

Key Words: K⁺ current • K_ATP • PIP₂ • Kir6.2 • PH domain

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. C. Koster, H. T. Kurata, D. Enkvetchakul, and C. G. Nichols DEND Mutation in Kir6.2 (KCNJ11) Reveals a Flexible N-Terminal Region Critical for ATP-Sensing of the KATP Channel Biophys. J., November 15, 2008; 95(10): 4689 - 4697. [Abstract] [Full Text] [PDF]

				O. Pochynyuk, Q. Tong, J. Medina, A. Vandewalle, A. Staruschenko, V. Bugaj, and J. D. Stockand Molecular Determinants of PI(4,5)P2 and PI(3,4,5)P3 Regulation of the Epithelial Na+ Channel J. Gen. Physiol., September 24, 2007; 130(4): 399 - 413. [Abstract] [Full Text] [PDF]

				A. Michailova, W. Lorentz, and A. McCulloch Modeling transmural heterogeneity of KATP current in rabbit ventricular myocytes Am J Physiol Cell Physiol, August 1, 2007; 293(2): C542 - C557. [Abstract] [Full Text] [PDF]

				J. D. Otero-Cruz, C. A. Baez-Pagan, I. M. Caraballo-Gonzalez, and J. A. Lasalde-Dominicci Tryptophan-scanning Mutagenesis in the {alpha}M3 Transmembrane Domain of the Muscle-type Acetylcholine Receptor: A SPRING MODEL REVEALED J. Biol. Chem., March 23, 2007; 282(12): 9162 - 9171. [Abstract] [Full Text] [PDF]

				D. Ma, X. D. Tang, T. B. Rogers, and P. A. Welling An Andersen-Tawil Syndrome Mutation in Kir2.1 (V302M) Alters the G-loop Cytoplasmic K+ Conduction Pathway J. Biol. Chem., February 23, 2007; 282(8): 5781 - 5789. [Abstract] [Full Text] [PDF]

				J. D. Brady, E. D. Rich, J. R. Martens, J. W. Karpen, M. D. Varnum, and R. L. Brown Interplay between PIP3 and calmodulin regulation of olfactory cyclic nucleotide-gated channels PNAS, October 17, 2006; 103(42): 15635 - 15640. [Abstract] [Full Text] [PDF]

				O. Pochynyuk, A. Staruschenko, Q. Tong, J. Medina, and J. D. Stockand Identification of a Functional Phosphatidylinositol 3,4,5-Trisphosphate Binding Site in the Epithelial Na+ Channel J. Biol. Chem., November 11, 2005; 280(45): 37565 - 37571. [Abstract] [Full Text] [PDF]

				L. Li, X. Geng, M. Yonkunas, A. Su, E. Densmore, P. Tang, and P. Drain Ligand-dependent Linkage of the ATP Site to Inhibition Gate Closure in the KATP Channel J. Gen. Physiol., August 29, 2005; 126(3): 285 - 299. [Abstract] [Full Text] [PDF]

				T. Lu, M.-P. Hong, and H.-C. Lee Molecular Determinants of Cardiac KATP Channel Activation by Epoxyeicosatrienoic Acids J. Biol. Chem., May 13, 2005; 280(19): 19097 - 19104. [Abstract] [Full Text] [PDF]

				K.-H. Park, J. Piron, S. Dahimene, J. Merot, I. Baro, D. Escande, and G. Loussouarn Impaired KCNQ1-KCNE1 and Phosphatidylinositol-4,5-Bisphosphate Interaction Underlies the Long QT Syndrome Circ. Res., April 15, 2005; 96(7): 730 - 739. [Abstract] [Full Text] [PDF]

				S. D. Silberberg, T.-H. Chang, and K. J. Swartz Secondary Structure and Gating Rearrangements of Transmembrane Segments in Rat P2X4 Receptor Channels J. Gen. Physiol., March 28, 2005; 125(4): 347 - 359. [Abstract] [Full Text] [PDF]

				V. G. Romanenko, Y. Fang, F. Byfield, A. J. Travis, C. A. Vandenberg, G. H. Rothblat, and I. Levitan Cholesterol Sensitivity and Lipid Raft Targeting of Kir2.1 Channels Biophys. J., December 1, 2004; 87(6): 3850 - 3861. [Abstract] [Full Text] [PDF]

				J. E. Manning Fox, C. G. Nichols, and P. E. Light Activation of Adenosine Triphosphate-Sensitive Potassium Channels by Acyl Coenzyme A Esters Involves Multiple Phosphatidylinositol 4,5-Bisphosphate-Interacting Residues Mol. Endocrinol., March 1, 2004; 18(3): 679 - 686. [Abstract] [Full Text] [PDF]

				D. Enkvetchakul and C.G. Nichols Gating Mechanism of KATP Channels: Function Fits Form J. Gen. Physiol., October 27, 2003; 122(5): 471 - 480. [Full Text] [PDF]

				Y.-W. Lin, T. Jia, A. M. Weinsoft, and S.-L. Shyng Stabilization of the Activity of ATP-sensitive Potassium Channels by Ion Pairs Formed between Adjacent Kir6.2 Subunits J. Gen. Physiol., July 28, 2003; 122(2): 225 - 237. [Abstract] [Full Text] [PDF]

				L. Garneau, H. Klein, L. Parent, and R. Sauve Contribution of Cytosolic Cysteine Residues to the Gating Properties of the Kir2.1 Inward Rectifier Biophys. J., June 1, 2003; 84(6): 3717 - 3729. [Abstract] [Full Text] [PDF]

				B. Ribalet, S. A. John, and J. N. Weiss Molecular Basis for Kir6.2 Channel Inhibition by Adenine Nucleotides Biophys. J., January 1, 2003; 84(1): 266 - 276. [Abstract] [Full Text] [PDF]

				Y. Guo, G. J. Waldron, and R. Murrell-Lagnado A Role for the Middle C Terminus of G-protein-activated Inward Rectifier Potassium Channels in Regulating Gating J. Biol. Chem., December 6, 2002; 277(50): 48289 - 48294. [Abstract] [Full Text] [PDF]

				C.A. Cukras, I. Jeliazkova, and C.G. Nichols The Role of NH2-terminal Positive Charges in the Activity of Inward Rectifier KATP Channels J. Gen. Physiol., August 26, 2002; 120(3): 437 - 446. [Abstract] [Full Text] [PDF]

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents